Spondyloepimetaphyseal dysplasia, Missouri type, metaphyseal anadysplasia 1, metaphyseal anadysplasia 2 and metaphyseal dysplasia, Spahr type:

Spondyloepimetaphyseal dysplasia, Missouri type (SEMD, Missouri type; MIM 602111) is an autosomal dominant disorder caused by missense mutations in the prodomain of matrix metalloproteinase 13 (MMP13). SEMD, Missouri type is allelic to metaphyseal anadysplasia 1 (MANDP1; MIM 602111) and they most likely represent a phenotypic spectrum rather than discrete disorders. Both SEMD, Missouri type and MANDP1 are disorders characterized by similar, if not identical, transient metaphyseal abnormalities including flaring, irregularity and a widened growth plate that improve spontaneously. Other findings include pear-shaped vertebrae in childhood, delayed bone age, rhizomelic shortening especially of the lower limbs, genu varum, tibial, femoral, radial and ulnar bowing, small flattened epiphyses and irregular endplates. An autosomal recessive form of MANDP1, caused by loss of function mutations in the MMP13 gene, also exists. A second autosomal recessive form of metaphyseal anadysplasia, designated metaphyseal anadysplasia 2 (MANDP2; MIM 613073), is caused by loss of function mutations in the matrix metalloproteinase 9 gene (MMP9). MANDP1 and MANDP2 are considered to be phenotypically indistinguishable. The dominant forms of SEMD, Missouri type / MANDP are considered to be more severe than the recessive forms.

Autosomal recessive mutations in MMP13 are causative of metaphyseal dysplasia, Spahr type (MIM 250400). This disorder is characterized by a normal birth length, but the development of bowed and shortened legs with a waddling gait in early childhood.

Copy number variation (CNV) analysis of the Metaphyseal anadysplasia genes is also offered as a panel. Additionally, CTGT offers a comprehensive test (both NGS and CNV panels) for these genes. Panel genes are also offered as individual sequencing and deletion/duplication tests unless otherwise indicated.